The autophagy receptor p62/SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy
The autophagy receptor p62/SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy
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DOI：
10.1038/s41467-019-13540-4
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发表时间：
2019-12-11
影响因子：
16.6
通讯作者：
Hansen, Malene
中科院分区：
文献类型：
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作者：
Kumsta, Caroline;Chang, Jessica T.;Hansen, Malene
自噬可以在选择性自噬受体如p62/SQSTM 1的帮助下降解货物，其促进泛素化货物的降解。虽然自噬过程与衰老有关，但选择性自噬在寿命调节中的影响仍不清楚。我们最近在秀丽隐杆线虫中发现，在激素性热休克后SQST-1/p62的转录水平增加，表明SQST-1/p62在应激反应和衰老中的作用。在这里，我们发现sqst-1/p62是热休克的激素益处所必需的，包括长寿，改善神经元蛋白质稳态和自噬诱导。此外，SQST-1/p62的过表达足以诱导不同组织中的自噬，延长寿命，并以自噬依赖性方式改善具有蛋白质稳态缺陷的突变体的适应性。总的来说，这些发现表明，增加选择性自噬受体的表达足以诱导自噬，增强蛋白质稳态和延长寿命，并证明sqst-1/p62在蛋白毒性应激反应中的重要作用。
Autophagy can degrade cargos with the help of selective autophagy receptors such as p62/SQSTM1, which facilitates the degradation of ubiquitinated cargo. While the process of autophagy has been linked to aging, the impact of selective autophagy in lifespan regulation remains unclear. We have recently shown in Caenorhabditis elegans that transcript levels of sqst-1/p62 increase upon a hormetic heat shock, suggesting a role of SQST-1/p62 in stress response and aging. Here, we find that sqst-1/p62 is required for hormetic benefits of heat shock, including longevity, improved neuronal proteostasis, and autophagy induction. Furthermore, overexpression of SQST-1/p62 is sufficient to induce autophagy in distinct tissues, extend lifespan, and improve the fitness of mutants with defects in proteostasis in an autophagy-dependent manner. Collectively, these findings illustrate that increased expression of a selective autophagy receptor is sufficient to induce autophagy, enhance proteostasis and extend longevity, and demonstrate an important role for sqst-1/p62 in proteotoxic stress responses.